Phosphatidylserine is said to be effective in improvement of brain functions such as cognitive dysfunction, mneme, and concentration, and it is known that its effects are further improved by binding it to DHA (docosahexaenoic acid). DHA-bonded phosphatidylserine is produced by extraction from bovine brains, but recently the production has not been performed due to the influence of mad cow disease. It is also known that the DHA-bonded phosphatidylserine can be synthesized by acting DHA-bonded phosphatidylcholine or DHA-bonded phosphatidylethanolamine with phospholipase D in the presence of serine (Patent Document 1). The DHA-bonded phosphatidylcholine, which is a starting material of the DHA-bonded phosphatidylserine, is extracted from tissues of fishes including a large amount of a polyunsaturated fatty acid, such as a tuna, a bonito, a mackerel, a sardine, a saury, and a horse mackerel, or eggs obtained from chickens raised with feed including a polyunsaturated fatty acid (Patent Document 1). A method using a mixture of phosphatidylserine derived from soybean and marine DHA-bonded phosphatidylserine (a serine-glycerophospholipid conjugate) is further known (Patent Document 2). In these methods, however, a starting material is expensive and the supply is unstable.
On the other hand, as a method for producing DHA-bonded phospholipid by bonding DHA to phospholipid, there is a method in which DHA is introduced into lysophospholipid obtained by hydrolyzing a fatty acid at 2-position of phospholipid using phospholipase A2, or commercially available lysophospholipid (Patent Document 3).
According to the method described in Patent Document 3, however, a significant amount of the phospholipase A2 remains because the phospholipase A2, which is used when the fatty acid at the 2-position of the phospholipid is hydrolyzed, is not removed, or inactivation operation thereof is not performed, and thus the DHA bonded to the lysophospholipid may sometimes be separated with time during storage. When the DHA-bonded phospholipid is serylated in accordance with the method described in Patent Document 1, there is a problem in which hydrolysis occurs at the 2-position during the reaction, because the serilation of phospholipase D with serine requires water; as a result, the DHA-bonded phosphatidylserine cannot be effectively synthesized.